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C. Year 3: Core Drugs > Direct oral anticoagulants (DOACs) - Vitamin K antagonists > Flashcards

Direct oral anticoagulants (DOACs) - Vitamin K antagonists Flashcards

1
Q

In secondary coagulation the extrinsic pathway is started when damaged endothelial cells release factor III (tissue factor III) which binds with the active factor VIIa (7a) and Ca2+. This then forms the VIIa-TF complex on the smooth muscle of blood vessels. The VIIa-TF complex then cleaves what factor?

1 - factor II (2 or prothrombin)
2 - factor X forming Xa
3 - factor VIII (8)
4 - factor V (5)

A

2 - factor X forming Xa

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2
Q

Once factor Xa has become active due to the extrinsic pathway, what factor does Xa (10a) and Ca2+ bind with that will then go onto form the prothrombinase complex?

1 - factor II (2 or prothrombin)
2 - factor I (1)
3 - factor VIII (8)
4 - factor V (5)

A

4 - factor V (5)

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3
Q

Once the prothrombinase complex has been formed by active factors X (10) and V (5), what does this then cleave in the extrinsic pathway?

1 - factor II (2 or prothrombin)
2 - factor I (1)
3 - factor VIII (8)
4 - factor XII (12)

A

1 - factor II (2 or prothrombin)
- prothrombin becomes thrombin (IIa)

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4
Q

Which pathway of the coagulation cascade doe the prothrombin time (PT), which is essentially the time it takes to form a clot measures?

1 - common
2 - extrinsic
3 - intrinsic

A

2 - extrinsic pathway

  • essentially this is the time it takes to form a clot
  • tissue factor (III), Ca2+ and factor VII (7) form complex and active factor X (10)
  • factor X (10) binds factor V (5) and Ca2+ and cleaves prothrombin into thrombin, which is where the name prothrombin time comes from
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5
Q

What is the normal value for prothrombin time (PT), which is essentially the time it takes to form a clot?

1 - 0.1 - 1.4 secs
2 - 1-4 secs
3 - 10-14 secs
4 - 15-20 secs

A

3 - 10-14 secs

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6
Q

In the coagulation cascade, activated partial thromboplastin time (aPTT) is a measure of which aspect of the coagulation cascade?

1 - common
2 - extrinsic
3 - intrinsic

A

3 - intrinsic

  • time it takes the intrinsic and common pathway to form a clot following the addition of calcium and phospholipid emulsion in-vitro
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7
Q

In the coagulation cascade, activated partial thromboplastin time (aPTT) is a measure of the intrinsic and common pathway to form a clot following the addition of calcium and phospholipid emulsion. What is the normal time for this?

1 - 0.1 - 1.4 secs
2 - 1-4 secs
3 - 10-14 secs
4 - 27-41 secs

A

4 - 27-41 secs

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8
Q

What is the international normalised ratio (INR)?

1 - measure of aPTT compared to age and gender matched aPTT
2 - measure of AP
3 - measure of PT as a ratio to a standardised or control PT

A

3 - measure of PT as a ratio to a standardised or control PT

  • PT is a measure of how long it takes clot to form
  • measures extrinsic pathway
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9
Q

The international normalised ratio (INR) is a measure of PT as a ratio to a standardised or control PT. What is a normal value for INR?

1 - 0.1 - 1.4
2 - 1-1.3
3 - 10-14
4 - 27-41

A

2 - 1-1.3

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10
Q

What is the purpose of the coagulation cascade?

1 - accentuate primary haemostasis
2 - convert fibrinogen into fibrin
3 - inhibit platelets activation in primary haemostasis

A

2 - convert fibrinogen into fibrin

  • fibrinogen = factor 1
  • fibrin = 1a
  • fibrin are monomers that form crosslinks and a strong clot
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11
Q

The coagulation cascade has 3 parts, intrinsic, extrinsic and common pathways. How is the intrinsic pathway started?

1 - factor XII (12) comes into contacts with collagen or activated platelets
2 - factor X (10) binds with fibrin
3 - factor XII (12) binds von willebrand factor
4 - factor XII (12) binds inactive platelets

A

1 - factor XII (12) comes into contacts with collagen or activated platelets

  • platelets are activated from primary haemostasis
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12
Q

Once the intrinsic pathway has begun by factor XII (12) binding with activated platelets or collagen, what then happens in the intrinsic pathway?

1 - factor XII (12) then becomes factor X (10)
2 - activated platelets activate factor XI
3 - factor XII (12) becomes factor XIIa (12a) and activates factor XI (11), then IX (9) and then X (10)
4 - collagen activates factor XI (11)

A

3 - factor XII (12) becomes factor XIIa (12a) and activates factor XI (11), then IX (9) and then X (10)

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13
Q

In the intrinsic pathway, which factor activates the common pathway?

1 - factor XIIa (12a)
2 - factor XIa (11a)
3 - factor IX (9)
4 - factor Xa (10a)

A

4 - factor Xa (10a)

  • Xa (10a) then activates factor II (2) called thrombin
  • factor II (2) called thrombin then activates factor I (1) which builds the fibrin mesh
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14
Q

Once the common pathway has been activates by factor Xa (10) it activates factor II (2 thrombin) which activates factor Ia (1a, called fibrin) which begins building fibrin. Which 4 other cofactors is factor IIa (2a thrombin) able to also activate?

1 - Ia (1a), IIIa (3a), IVa (4a) and V (5a)
2 - XIa (11a), IIIa (3a), IVa (4a) and VIIa (7a)
3 - IIIa (3a), IVa (4a), Va (5a) and XIIa (12a)
4 - Va (5a), VIIIa (8a), IXa (9a) and XIIIa (13a)

A

4 - Va (5a), VIIIa (8a), IXa (9a) and XIIIa (13a)

  • Va (5a) acts as a cofactor for factor Xa (10a)
  • VIIIa (8a) acts as a cofactor for factor IXa (9a)
  • IXa (9a)
  • XIIIa (13a) helps factor I (1a) called fibrin form crosslinks and a stronger clot
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15
Q

The extrinsic pathway is activated when factor VIIa (7a) binds with what on exposed tissue?

1 - von Willebrand factor
2 - tissue factor
3 - tissue plasminogen factor
4 - protein C

A

2 - tissue factor

  • factor VIIa (7a) then activates the factor Xa (10a) and the common pathway
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16
Q

In secondary haemostasis, which factor is often referred to as the accelerator due to its multiple procoagulating functions?

1 - factor IIa (2a)
2 - factor Xa (10a)
3 - factor Va (5a)
4 - factor Ia (1a)

A

1 - factor IIa (2a)
- also referred to as thrombin

17
Q

Thrombin (factor IIa (2a) is able to do lots of things involved in coagulation. It does all of the following EXCEpt which one?

1 - binds platelets activating them
2 - activates factor Va (5a)
3 - activates factor VIIIa (8a)
4 - converts fibrinogen (factor I (1) into fibrin (factor Ia (1a))
5 -converts factor XIII (13) into factor XIIIa (13a) that binds with Ca2+ cofactor forming cross bridges between fibrin mesh
6 - activates protein C and S

A

6 - activates protein C and S

  • proteins S and C ensure clotting does not go into overdrive
18
Q

Factor IIa (2a) also called thrombin is one of the key cofactors in secondary haemostasis. What is the bodies natural molecule that aims to modulate the activation of thrombin?

1 - protein S
2 - protein C
3 - antithrombin (factor IIIa (3a))
4 - factor Va (5a)

A

3 - antithrombin (factor IIIa (3a))

19
Q

Factor IIa (2a) also called thrombin is one of the key cofactors in secondary haemostasis. Antithrombin (factor IIIa (3a)) is the bodies naturally produced modulator of thrombin. Which 2 key factors in the common pathway is antithrombin (factor IIIa (3a)) able to bind with and reduce coagulation?

1 - factors Va (5a) and Xa (10a)
2 - factors IIa (2a) and Xa (10a)
3 - factors XIIIa (8a) and Xa (10a)
4 - factors IIa (2a) and XIIIa (13a)

A

2 - factors IIa (2a) and Xa (10a)

  • this essentially inhibits or reduces the activity of the common pathway
  • factor Xa converts prothrombin into thrombin (factor IIa (2a))
  • remember 2 = 7 = 9, 10, 11, 12
20
Q

Which factors overall is anti-thrombin (IIIa (3a)) able to bind with and inhibit?

1 - factors 1, 2, 3, 4 and 5
2 - factors 2, 7, 9, 10, 11 and 12
3 - factors 1, 2, 7, 9 and 10
4 - factors 5, 7, 9, 11, 13

A

2 - factors 2, 7, 9, 10, 11 and 12

  • remember 2 = 7 = 9, 10, 11, 12
21
Q

Which factors in the coagulation cascade are synthesised in the liver are vitamin K dependent?

1 - 2, 3, 4 and 5
2 - 2, 7, 9 and 10
3 - 2, 4, 6 and 8
4 - 2, 7, 10 and 12

A

2 - 2, 7, 9 and 10

22
Q

Warfarin is the core vitamin K antagonist we need to know about. Which factors of the coagulation cascade is Warfarin able to inhibit?

1 - 2, 3, 4 and 5
2 - 2, 7, 9 and 10
3 - 2, 4, 6 and 8
4 - 2, 7, 10 and 12

A

2 - 2, 7, 9 and 10

  • inhibits vitamin K factors II (2), VII (7), IX 9 and X (10) - coagulation
  • 1972 was the year of diSCo
  • factors 9, 7, 2 and 10
  • proteins S and C
23
Q

Warfarin is able to inhibit the synthesis of factors 2, 7, 9 and 10 in the coagulation cascade. However, what enzyme is Warfarin able to inhibit to cause an anti-coagulability state?

1 - vitamin K hydroquinone
2 - glutamyl carboxylase
3 - vitamin K epoxide reductase
4 - quinone reductase

A

3 - vitamin K epoxide reductase

  • essentially stops the recycling of vitamin K
24
Q

In addition to inhibiting factors 2, 7, 9 and 10, what 2 other proteins is Warfarin able to inhibit?

1 - albumin
2 - protein S
3 - protein C
4 - fibrinogen

A

2 - protein S
3 - protein C

  • 1972 was the year of diSCo
  • factors 9, 7, 2 and 10
  • proteins S and C
25
Q

Warfarin is indicated in all of the following EXCEPT?

1 - PE
2 - DVT
3 - ACS
4 - AF

A

3 - ACS

  • PE and DVT make up venous thromboembolism (VTE)
  • DOACs are the generally preferred over Warfarin
26
Q

In which of the following is Warfarin preferred as the 1st choice medication?

1 - mechanical heart valves
2 - AF
3 - atrial flutter
4 - ACS

A

1 - mechanical heart valves

27
Q

Which of the following is the key adverse event of Warfarin?

1 - anaemia
2 - GI upset
3 - dizziness
4 - bleeding
5 - elevated liver enzymes

A

4 - bleeding

  • contraindicated if active bleeding is present
28
Q

What is the antidote of Warfarin?

1 - naloxone
2 - acetylcysteine
3 - flumazenil
4 - phytomenadione

A

4 - phytomenadione

  • naloxone = opioid antidote
  • acetylcysteine = paracetamol overdose on liver
  • flumazenil = benzodiazepine overdose
29
Q

Warfarin is not effective immediately. There is typically a lag between the dose and effect. How long is this typically?

1 - 24h
2 - 24-48h
3 - 3-4 days
4 - 7 days

A

3 - 3-4 days

30
Q

Why are warfarins not generally used in patients with liver disease?

1 - blood flow will be impaired
2 - cannot remove warfarin and it can become toxic
3 - coagulation factors will already be depleted

A

3 - coagulation factors will already be depleted

  • this would amplify the anti-coagulation effect of warfarin
31
Q

Why is warfarin not recommended for women pregnancy in the 1st trimester?

1 - teratogenicity
2 - cross placenta and cause blood thinning in foetus
3 - can be passed through breast milk
4 - increases risk of rhesus positive

A

1 - teratogenicity

  • leads to deformity in babies
32
Q

Warfarin is metabolised by cytochrome P450 (CYP). Which of the following are CYP inducers, which effectively increasing the risk of clotting?

1 - phenytoin
2 - carbamazepine
3 - rifampicin
4 - all of the above

A

4 - all of the above

  • phenytoin = epilepsy medication
  • carbamazepine = anticonvulsant medication
  • rifampicin = antibiotic
33
Q

Warfarin is metabolised by cytochrome P450 (CYP). Which of the following are CYP inhibitor, which effectively increases the risk of bleeding?

1 -fluconazole
2 - macrolids
3 - verapamil
4 - all of the above

A

4 - all of the above

  • fluconazole = anti-fungal medication
  • macrolids = antibiotic class
  • verapamil = Ca2+ channel blocker
34
Q

In addition to macrolids and rifampicin, other antibiotics can aaccentuate the effects of warfarin, but not by affecting cytochrome P450 (CYP). How else can other antibiotics affect warfarin efficacy?

1 - inhibit absorption of vitamin K
2 - kill off healthy flora, reducing absorption of vitamin K
3 - increase risk of diarrhoea

A

2 - kill off healthy flora, reducing absorption of vitamin K

35
Q

When administering Warfarin, it can initially making clotting worse, generally in the first 36 hours. Why is this the case?

1 - liver becomes hypersensitive to vitamin K
2 - toxicity damages coagulation proteins
3 - warfarin takes a long time to metabolise
4 - inhibits proteins S and C

A

4 - inhibits proteins S and C

  • proteins S and C inhibit Va and VIIIa
  • basically means patients may be at increase risk of clot in this 36 hour window
  • heparin can be used to help with this
36
Q

Which of the following needs to be monitored to alter the patients warfarin dose and efficacy?

1 - AP
2 - aPTT
3 - INR

A

3 - INR
- measures extrinsic pathway
- INR = PT/normal PT

  • warfarin effects factor VIIa (7a) first, a measure of the extrinsic pathway through factor VIIa
37
Q

What is considered a normal INR in patients taking warfarin?

1 - 0.1-1
2 - 1.0-1.3
3 - 2.0-3.0
4 - 5.0-10.0

A

3 - 2.0-3.0

C. Year 3: Core Drugs (125 decks)

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